This research proposal involves the long term development and application of an artificial support system that could be used in the treatment of acute reversible hepatic failure and in conjunction with hepatic transplantation. Animal models of acute liver failure will be investigated so as to develop a tool for attempts to (1) gain insights into the biochemical nature of the metabolic coma, and (2) evaluate critically, and in a controlled manner, various therapeutic endeavors. Acetaminophen induced hepatic necrosis in several species will be studied to ascertain whether acute liver failure can be reproducibly obtained, and thus have a potentially reversible model which would simulate the clinical condition seen in acetaminophen overdose. The ischemic model of liver failure will also be evaluated. Support systems, such as hemodialysis, resin hemoperfusion and coated-charcoal hemoperfusion will be tested for their effect on coma and survival under experimental conditions. If such devices or combinations thereof can be found to be strikingly beneficial to animal models in acute liver failure, then a controlled trial in humans would be indicated.